{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:03:16Z","timestamp":1789966996046,"version":"4.0.1"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to clarify the relationship between obstructive sleep apnea (OSA) and Alzheimer's disease (AD)-related biomarkers\u2014specifically amyloid \u03b2 (A\u03b2) and tau proteins\u2014in blood and cerebrospinal fluid (CSF) through a systematic review and meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PubMed, Web of Science (WOS), Embase, and Cochrane Library were searched from database inception to December 30, 2024 (PROSPERO registration: CRD420251148709). Studies reporting blood or CSF levels of A\u03b240, A\u03b242, total A\u03b2 (\n                      <jats:italic>T<\/jats:italic>\n                      -A\u03b2), total tau (\n                      <jats:italic>T<\/jats:italic>\n                      -tau), or phosphorylated tau (\n                      <jats:italic>P<\/jats:italic>\n                      -tau) in patients with OSA vs. non-OSA controls were included. A random-effects model was employed for all meta-analyses. The risk of bias was assessed using appropriate validated tools.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen studies (seven blood, six CSF) were included. In blood, OSA patients showed significantly higher\n                      <jats:italic>T<\/jats:italic>\n                      -A\u03b2 (SMD = 0.66, 95% CI [0.34, 0.97],\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 0%,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) and\n                      <jats:italic>T<\/jats:italic>\n                      -tau (SMD = 1.48, 95%\n                      <jats:italic>C<\/jats:italic>\n                      I [0.33, 2.62],\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 93.6%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.011). No significant differences were found for blood A\u03b240, A\u03b242, A\u03b242\/A\u03b240 ratio, or\n                      <jats:italic>P<\/jats:italic>\n                      -tau. In CSF, patients with OSA had significantly lower A\u03b240 (SMD = \u22121.13, 95% CI [\u22121.65, \u22120.60],\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 0%,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) and A\u03b242 (SMD = \u22121.23, 95% CI [\u22121.84, \u22120.63],\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 77.3%,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01), but no differences in A\u03b242\/A\u03b240 ratio,\n                      <jats:italic>T<\/jats:italic>\n                      -tau, or\n                      <jats:italic>P<\/jats:italic>\n                      -tau.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>High heterogeneity, pre-dominantly cross-sectional designs, low-to-very-low GRADE certainty for most outcomes, retrospective registration, and limited study numbers preclude causal inference and warrant cautious interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This exploratory meta-analysis revealed compartment-specific associations between certain AD-related biomarkers and OSA. However, given the low-to-very-low certainty of the available evidence and the substantial uncertainty reflected by prediction intervals that frequently crossed the null value, these findings should be regarded as hypothesis-generating rather than conclusive. Notably, the absence of consistent alterations in\n                      <jats:italic>P<\/jats:italic>\n                      -tau or the CSF A\u03b242\/A\u03b240 ratio argues against a direct signature of established AD neuropathology. Future rigorously designed, large-scale prospective studies are warranted to determine whether these biomarker changes reflect early AD pathology or reversible physiological responses to OSA-related hypoxia and sleep fragmentation.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Systematic review registration:<\/jats:bold>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?RecordID=1148709<\/jats:ext-link>\n                      , identifier CRD420251148709.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1817426","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:28:00Z","timestamp":1789964880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between obstructive sleep apnea and Alzheimer's disease-related biomarkers (amyloid-\u03b2 and tau) in blood and cerebrospinal fluid: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]},{"name":"The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligeer","family":"Che","sequence":"additional","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]},{"name":"The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Su","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbin","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00043.2008","article-title":"Pathophysiology of sleep apnea","volume":"90","author":"Dempsey","year":"2010","journal-title":"Physiol Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"049","DOI":"10.1055\/s-2002-32318","article-title":"O'connor G, Nieto J. 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